The structural and functional alterations of vascular endothelium caused by fluid shear stress will be investigated in vitro using cultured endothelial cells and a special apparatus we have developed for producing controlled fluid shear stress. The apparatus utilizes a shallow cone rotating above a flat plate to produce shear stresses between 10 to the -2 and 200 dynes/cm2; both laminar and turbulent flow conditions can be checked. Additional modifications will provide oscillating and alternating shear stress levels to investigate the response of the cells to shear conditions approximating those existing in vivo. Specific parameters of endothelial structure and function to be measured include: growth patterns and growth kinetics; migration and mitosis following injury; cell orientation and morphology; rates and mechanisms of endocytosis; cytoskeletal organization; and interaction with extracellular matrix. This is a collaborative research effort that draws upon the resources, expertise, and experience of the Fluid Mechanics Laboratory, Massachusetts Institute of Technology and the Vascular Pathophysiology Laboratory, Brigham and Women's Hospital. The research system to be used in this program, comprised of an accurately controlled fluid shear stress apparatus and well defined cultured endothelial specimens, should yield valuable information on the influence of fluid shear stress on the structure and function of vascular endothelium. Such information would provide new insights into vascular physiology and the pathogenesis of vascular diseases such as atherosclerosis.